Devices and methods utilizing arrays of structures for analyte capture

• US 5,707,799 A
• Filed: 09/30/1994
• Issued: 01/13/1998
• Est. Priority Date: 09/30/1994
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Lowery, Michael G., Shain, Eric B., Oosta, Gary M., Schapira, Thomas G., Loomis, Neil W., Grace, John P., Hansmann, Douglas D.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/315,364
• Time in Patent Office: 1,201 Days
• Field of Search: 422/55, 422/56, 422/57, 422/58, 422/101, 435/6, 435/7.2, 435/7.9, 435/7.92, 435/7.93, 435/7.94, 435/7.5, 435/287.1, 435/287.2, 435/287.3, 435/288.2, 435/810, 436/514, 436/518, 436/527, 436/531, 436/164, 436/172, 436/804, 436/805, 436/809, 436/810
• US Class Current: 435/6.11
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C08G 18/0866 the dispersing or dispersed phase being an aqueous medium
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: G01N 33/5304 Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 436/804 Radioisotope, e.g. radioimmunoassay
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

The present invention relates to analytical devices for determining the presence or amount of an analyte in a test sample. The analytical devices comprise an inlet port, a vent, a channel, and an array of structures. The structures have immobilized reagent covalently or non-covalently attached to the surface of the structures. The immobilized reagent captures analyte in the test sample where it is detected by a detection system. The present invention also provides methods and reagents for performing assays utilizing the analytical devices of the present invention. The present invention also provides methods of manufacturing the analytical devices of the present invention.

Claims

1. An analytical device for determining the presence or an amount of an analyte in a test sample comprising, in combination:

a base layer;

an array of structures arising from said base layer, each of said structures having a surface providing immobilized reagent, said immobilized reagent covalently or non-covalently attached to said surface of said structure, said immobilized reagent capable of binding a member selected from the group consisting of analyte, analyte-analog, ancillary binding member, and labelled reagent; and

a plurality of channels adjacent to said structures, wherein said test sample containing said analyte, analyte-analog, ancillary binding member, or labelled reagent flows through said channels, said analyte, analyte-analog, ancillary binding member, or labelled reagent diffusing across the width of said channels binding to said immobilized reagent, wherein the ratio of the height of said structures to the average width of said channels is greater than 2;

1.

2. The analytical device of claim 1 wherein said analyte and said immobilized reagent comprises an antigen and an antibody.

3. The analytical device of claim 1 wherein said analyte and said immobilized reagent comprises complementary nucleotide sequences.

4. The analytical device of claim 1 wherein said analyte and said immobilized reagent comprises a lectin and a carbohydrate.

5. The analytical device of claim 1 wherein said analyte and said immobilized reagent comprises an avidin and a biotin.

6. The analytical device of claim 1 wherein said structures are made with copolymers, blends, laminates, metallized foils, metallized films or metals deposited on a material selected from the group consisting of:

polyolefins, polyesters, styrene containing polymers, polycarbonate, acrylic polymers, chlorine containing polymers, acetal homopolymers and copolymers, cellulosics and their esters, cellulose nitrate, fluorine containing polymers, polyamides, polyimides, polyetheretherketone, sulfur containing polymers, polyurethanes, silicon containing polymers, glass, and ceramic materials.

7. The analytical device of claim 1 wherein said structures can have a height ranging from about 1 micrometer to about 1 millimeter.

8. The analytical device of claim 1 wherein said structures can have an average width ranging from about 1 micrometer to about 1 millimeter.

9. The analytical device of claim 1 wherein said channel has a depth ranging from about 1 micrometer to about 1 millimeter.

10. The analytical device of claim 1 wherein said channel has an average width ranging from about 0.02 micrometers to about 20 micrometers.

11. The analytical device of claim 1 wherein said structures in said array of structures are similarly shaped.

12. The analytical device of claim 11 wherein said similarly shaped structures are selected from the group consisting of:

diamonds, hexagons, octagons, rectangles, squares, circles, semi-circles, triangles and elipses.

13. The analytical device of claim 11 wherein said array of structures are staggered relative to the direction of test sample flow.

14. The analytical device of claim 1 further comprising a labelled reagent, said labelled reagent comprising a detectable label and a specific binding member which is specific for said analyte, analyte-analog, or ancillary binding member.

15. The analytical device of claim 1 wherein a detectable label is added to said analytical device, said detectable label is selected from the group consisting of:

non-radioactive isotopes, metal chelators, and direct visual labels.

16. The analytical device of claim 1 wherein said device is a cuvette.

17. The analytical device of claim 1 wherein said device is a dipstick.

18. The analytical device of claim 1 further comprising a separator anterior to said structures.

19. The analytical device of claim 18 wherein said separator is a hydrophilic sintered porous matrix.

20. The analytical device of claim 19 wherein said matrix is treated with a red blood cell agglutinating agent.

21. The analytical device of claim 1 wherein said device has a control means.

22. The analytical device of claim 1 wherein said array of structures have multiple immobilized reagents to test for multiple analytes in said test sample.

23. The analytical device of claim 1 wherein differential pressure is used to drive said test sample through the device.

24. The analytical device of claim 1 wherein chambers are added to said device anterior or posterior to said array of structures.

25. The analytical device of claim 1 wherein said device has at least one alternate pathway.

26. The anaytical device of claim 25 wherein said alternate pathway transports said test sample to a separate array of structures.

27. The analytical device of claim 1 wherein said ancillary binding member binds to said analyte, and said analyte binds to said immobilized reagent.

28. The analytical device of claim 1 wherein said structures and channels of said devices are manufactured by at least one of the following steps:

lasering, micromachining, photolithography, reactive ion etching, ion beam milling, embossing, electroforming, electroplating, injection molding, compression molding, casting, or reaction injection molding.

29. The analytical device of claim 28 wherein said direct visual labels are selected from the group consisting of fluorescent signals, chemiluminescent signals, and enzymatic signals.

30. An analytical device for determining the presence or an amount of an analyte in a test sample comprising, in combination:

a base layer;

an inlet port and a vent;

an array of structures arising from said base layer, each of said structures having a surface providing a capture site for said analyte;

an immobilized reagent, said immobilized reagent covalently or non-covalently attached to said surface of said structure, said immobilized reagent capable of binding an a member selected from the group comprising;

analyte, analyte-analog, and an ancillary binding member;

a plurality of channels adjacent to said structures, wherein said test sample containing said analyte, analyte-analog, or ancillary binding member flows through said channels, said analyte, analyte-analog, or ancillary binding member diffusing across the width of said channels to bind said immobilized reagent; and

a labelled reagent comprising a specific binding member conjugated to a detectable label, said detectable label capable of producing a signal at said capture site, said signal indicating the presence or amount of said analyte present in said test sample, wherein the ratio of the height of said structures to the average width of said channels is greater than 2;

1.